We propose a P30 center to enhance and extend the effectiveness of currently funded human laboratory and treatment clinical research on the clinical pharmacology and pharmacotherapy of abused drugs. Our approach is multi-disciplinary, including investigators from psychiatry, psychopharmacology, clinical psychology, neurology, general internal medicine and clinical pharmacology, toxicology, dermatology, genetics, pediatrics, pharmacy, organic, medicinal and analytical chemistry, and statistics. The research focuses on the clinical pharmacology and pharmacotherapy of stimulant drugs; cocaine, methamphetamine, and nicotine. Individually funded projects enhanced the center's core resources include studies of the pharmacokinetics and pharmacodynamics of nicotine, nicotine kinetics in twin studies to investigate genetic susceptibility to nicotine addiction, pharmacokinetics of cocaine and methamphetamine in skin and hair with particular attention to understanding mechanisms for individual differences, innovative pharmacotherapies for cocaine addiction, and isradipine pharmacotherapy for methamphetamine addiction. The research involves only human subjects. This application requests support for a shared administrative and laboratory research infrastructure. Our aims are: 91) To provide a state-of-the-art analytical and synthetic chemistry resource for collaborative projects. (2) To provide administrative coordination and a resource for preparation of manuscripts, IRB submissions, grant applications fro data processing, and report preparation, coordination of research seminars, and other teaching and communication activities, grant management, and to carry out other administrative services required by the research teams. (3) To provide statistical services, particularly advice on study design and data analysis. The aim of the P30 center is to provide a facility with adequate administrative and scientific resources with stability of support and continuity as individually funded scientific projects change and evolve over time. This facility will be a cost-effective shared resource and will foster a synergistic approach and enhanced funded research to further our understanding of the clinical pharmacology of human psychoactive drug use, its health consequences and its management.